Photodynamic therapy (PDT) is a process whereby light of a specific wavelength or waveband is directed to tissues undergoing treatment or investigation, which have been rendered photosensitive through the administration of a photoreactive or photosensitizing agent. Thus, in this therapy, a photoreactive agent having a characteristic light absorption waveband is first administered to a patient, typically by intravenous injection, oral administration, or by local delivery to the treatment site. Abnormal tissue in the body is known to selectively absorb certain photoreactive agents to a much greater extent than normal tissue. Once the abnormal tissue has absorbed or linked with the photoreactive agent, the abnormal tissue can then be treated by administering light of an appropriate wavelength or waveband corresponding to the absorption wavelength or waveband of the photoreactive agent. Such treatment can result in the necrosis of the abnormal tissue.
PDT has proven to be very effective in destroying abnormal tissue such as cancer cells and has also been proposed for the treatment of vascular diseases, such as atherosclerosis and restenosis due to intimal hyperplasia. In the past percutaneous transluminal coronary angioplasty (PTCA) has typically been performed to treat atherosclerotic cardiovascular diseases. A more recent treatment based on the use of drug eluting stents has reduced the rate of restenosis in some diseased vessels. As effective as such therapies are, a new platform of therapy is needed for treating peripheral arterial disease and more problematic coronary diseases, such as vulnerable plaque, saphenous vein bypass graft disease, and diffuse long lesions.
The objective of PDT may be either diagnostic or therapeutic. In diagnostic applications, the wavelength of light is selected to cause the photoreactive agent to fluoresce, thus yielding information about the tissue without damaging the tissue. In therapeutic applications, the wavelength of light delivered to the tissue treated with the photoreactive agent causes the photoreactive agent to undergo a photochemical reaction with oxygen in the localized tissue, to yield free radical species (such as singlet oxygen), which cause localized cell lysis or necrosis. The central strategy to inhibit arterial restenosis using PDT, for example, is to cause a depletion of vascular smooth muscle cells, which are a source of neointima cell proliferation (see, Nagae et al., Lasers in Surgery and Medicine 28:381–388, 2001). One of the advantages of PDT is that it is a targeted technique, in that selective or preferential delivery of the photoreactive agent to specific tissue enables only the selected tissue to be treated. Preferential localization of a photoreactive agent in areas of arterial injury, with little or no photoreactive agent delivered to healthy portions of the arterial wall, can therefore enable highly specific PDT ablation of arterial tissue.
Light delivery systems for PDT are well known in the art. Delivery of light from a light source, such as a laser, to the treatment site has been accomplished through the use of a single optical fiber delivery system with special light-diffusing tips affixed thereto. Exemplary prior art devices also include single optical fiber cylindrical diffusers, spherical diffusers, micro-lensing systems, an over-the-wire cylindrical diffusing multi-optical fiber catheter, and a light-diffusing optical fiber guidewire. Such prior art PDT illumination systems generally employ remotely disposed high power lasers or solid state laser diode arrays, coupled to optical fibers for delivery of light to a treatment sight. The disadvantages of using laser light sources include relatively high capital costs, relatively large size, complex operating procedures, and the safety issues inherent when working with high power lasers. Accordingly, there is a tremendous need for a light generating system that requires no lasers, and which generates light at the treatment site. For vascular application of PDT, it would be desirable to provide a light-generating apparatus having a minimal cross-section, a high degree of flexibility, and compatibility with a guidewire, so the light-generating apparatus can be delivered to the treatment site. Such an apparatus should provide a light uniformly to the treatment area.
For vascular application of PDT, it would be further desirable to provide a light-generating apparatus configured to be centered within a blood vessel, and which is configured to remove light absorbent material, such as blood, from the light path between the target tissue and the apparatus. Typically, centering of apparatus within a vessel can be achieved with an inflatable balloon catheter that matches the diameter of the blood vessel when the balloon is inflated. Such devices desirably occlude blood flow, enabling the light path to remain clear of obstructing blood. However, a single balloon is not sufficient to treat lesions in coronary blood vessels that are greater than about 30 mm in length, because a single inflated balloon may not provide good centering of the apparatus within such a long section. Therefore, it would be desirable to provide a light-generating apparatus that is configured treat long lesions or long vessel segments.